Activities of the principal brain vesicular monamine transporter, VMAT2, are key to understanding the cellular compartmentalization of monoamines that may play a key role in modulating the actions and neurotoxicities induced by amphetamine and by each of the toxins that selectively kills dopaminergic neurons to provide the best current models of Parkinson's disease. In this FY, workers in this Branch described the properties of knockout mice with deletions of the VMAT2 gene, as well as the structure of this gene itself in mice and humans. VMAT2 deficient heterozygote mice show selective alterations in their responses to cocaine and amphetamine, as well as differences in MPTP toxicities. These mice substantially enhance our understanding of mechanisms of psychostimulant and dopaminergic neurotoxin action.